The effect of fluid balance on outcomes in patients with sepsis; experience of a tertiary hospital
Sepsisli hastalarda sıvı dengesinin sonuçlara etkisi; üçüncü basamak bir hastane deneyimi
Deniz Uysal Sönmez, Hülya Dirol, Abdullah Erdoğan
Deniz Uysal Sönmez, Chest Physiotherapist, Akdeniz University Hospital, Chest Department, Antalya, Turkey, e-mail: denizuysalsonmez@
hotmail.com (https://orcid.org/0000-0001-7168-361X)
Hülya Dirol, M.D. Pulmonolog, Ass. Prof. Akdeniz University Hospital Chest Department, Dumlupınar Boulevard Akdeniz University Hospital, Antalya, Turkey, e-mail: hulyadirol@akdeniz.edu.tr (https://orcid.org/0000-0002-7712-6467) (Corresponding Author)
Abdullah Erdoğan, M.D. Professor, Akdeniz University Hospital, Chest Surgery Department, Antalya, Turkey, e-mail: abdullaherdogan@
akdeniz.edu.tr (https://orcid.org/0000-0002-5299-441X)
Purpose: Fluid replacement is vital for stabilizing hemodynamic status in sepsis. However, the positive fluid balance may result in pulmonary edema and may be associated with increased mortality.
Materials and methods: This is a single-center, retrospective study in which the patients, supported with mechanical ventilation (MV) due to sepsis, were enrolled. All the data about the demographic features, medications, MV duration, vital signs, blood gas analysis, blood tests, the fluid balance were obtained from the patient files and nursing reports. Patients were subclassed positive, negative and balanced according to fluid balance and compared to each other.
Results: A total of fifty patients with sepsis were included in the study. Twenty-six (52%) of the patients were male and the mean age was 66.58±3.25 years. The mortality rate was 90%. The mean fluid intake and output were 3481.8±1002.7, 1877.6±921.3 milliliters, respectively. Forty-two (84%) were in positive fluid balance, 6 (12%) in negative fluid balance, and 2 (4%) in balance. There was no significant difference between the fluid balance subgroups in terms of length of stay in the ICU, duration of mechanical ventilation, and mortality. The use of diuretics was significantly higher in patients with positive fluid balance (p=0.023). CRP was significantly higher while serum albumin was lower in patients with positive fluid balance (respectively, p=0.003, p=0.034).
There was no difference between the mean GCS, SOFA scores of survivors and nonsurvivors but the mean APACHE II scores in nonsurvivors were significantly higher than in survivors (p=0.026).
Conclusion: Our study showed that positive fluid balance did not affect the length of stay in the ICU, duration of mechanical ventilation and mortality, and that APACHE II was better than SOFA and GCS in predicting mortality.
Key words: Fluid therapy, sepsis, shock, mechanical ventilation, intensive care.
Uysal Sonmez D, Dirol H, Erdoğan A. The effect of fluid balance on outcomes in patients with sepsis; experience of a tertiary hospital. Pam Med J 2022;15:87-94.
ÖzAmaç: Sıvı replasmanı, sepsiste hemodinamik durumu stabilize etmek için hayati öneme sahiptir. Bununla birlikte, pozitif sıvı dengesinin olumsuz etkileri olabilir.
Gereç ve yöntem: Ağustos 2016-Nisan 2017 tarihleri arasında üçüncü basamak bir hastanede sepsise bağlı mekanik ventilasyonla desteklenen hastaları içeren tek merkezli, retrospektif bir çalışmadır. Demografik özellikler, ilaçlar, mekanik ventilasyon süresi, yoğun bakımda kalış süresi, kan biyokimyasal testleri, sıvı dengesi ile ilgili tüm veriler hasta dosyaları ve hemşire çizelgelerinden elde edildi. Hastalar sıvı dengesine göre pozitif, negatif ve dengeli olarak alt sınıflandırılarak birbirleriyle karşılaştırıldı.
Bulgular: Çalışmaya toplam 50 sepsisli hasta alındı. Hastaların yirmi altısı (%52) erkekti ve yaş ortalaması 66,58±3,25 yıl idi. Ölüm oranı %90 idi. Ortalama sıvı alımı ve çıkışı sırasıyla 3481,8±1002,7, 1877,6±921,3 mililitre idi. Kırk ikisi (%84) pozitif sıvı dengesinde, 6'sı (%12) negatif sıvı dengesinde ve 2'si (%4) dengede idi. Sıvı dengesi alt grupları arasında yoğun bakımda kalış süresi, mekanik ventilasyon süresi ve mortalite açısından anlamlı fark yoktu. Pozitif sıvı dengesi olan hastalarda diüretik kullanımı anlamlı olarak daha yüksekti (p=0,023). Pozitif sıvı dengesi olan hastalarda CRP anlamlı olarak daha yüksek, serum albümini ise daha düşüktü (sırasıyla, p=0,003, p=0,034). Sağ kalanların ve sağ kalmayanların ortalama GCS, SOFA skorları arasında fark yoktu ancak sağ kalmayanlarda ortalama APACHE II skorları sağ kalanlardan anlamlı derecede yüksekti (p=0,026).
Sonuç: Çalışmamız, pozitif sıvı dengesinin yoğun bakımda kalış süresi, mekanik ventilasyon süresi ve mortaliteyi etkilemediğini ve APACHE II'nin mortaliteyi öngörmede SOFA ve GKS'ye göre daha iyi olduğunu gösterdi.
Anahtar kelimeler: Sıvı tedavisi, sepsis, şok, mekanik ventilasyon, yoğun bakım.
Uysal Sönmez D, Dirol H, Erdogan A. Sepsisli hastalarda sıvı dengesinin sonuçlara etkisi; üçüncü basamak bir hastane deneyimi. Pam Tıp Derg 2022;15:87-94.
Gönderilme tarihi:17.05.2021 Kabul tarihi:28.07.2021
Introduction
Sepsis is a syndrome characterized by organ dysfunction, hypoperfusion, and hypotension due to infection [1]. Although treatment options for sepsis have improved over the years, the mortality rate is still quite high [2]. Various factors related to mortality in sepsis have been reported so far [3]. Fluid replacement therapy is supposed to improve tissue oxygenation and stabilize the hemodynamic status and thereby decrease mortality in sepsis. However, results regarding the effect of this treatment on mortality are contradictory. Moreover, the concern is also common that excessive fluid replacement in sepsis will lead to increased hydrostatic pressure in vessels prone to extravasation due to increased vascular permeability and, consequently, pulmonary edema and this may increase the length of mechanical vantilation and hospital stay and even mortality.
In this study, we evaluated the effect of fluid balance on the patients supported by mechanical ventilation due to sepsis.
Methods
Study population
The patients, supported with invasive mechanical ventilation due to sepsis or septic shock between August 2016 and April 2017 in the intensive care unit of Akdeniz University Hospital, were involved in the study. The patients with chronic heart failure and/or chronic renal failure and who stayed lesser than 72 hours in ICU, were excluded from the study. All the data about the demographic features, medications, IMV duration and modes, sedation supports, vital signs, blood gas analysis, blood tests, the fluid balance were obtained from the patients’
files, nurse observation charts, and intensive care unit electronic records. APACHE II score, Glasgow coma score (GCS) and Sequential organ failure assessment (SOFA) score in the first 24-hour were used in the study.
We used “The Third International Consensus
vomiting, and the amount of fluid obtained during dialysis) and then we classified them according to the fluid balance. The classification criteria were as follows i) positive fluid balance;
intake was at least more than 400 ml higher than output. ii) negative fluid balance; output was at least more than 400 ml higher than intake. iii) balanced; intake was <400 ml higher than output or equal to output.
The study was approved by the Clinical Research Ethics Committee of Akdeniz University Medical Faculty. Written informed consent was obtained from all participants.
Statistical analysis
For the statistical analysis, Statistical Package for Social Science (SPSS) 21.0 was used. Descriptive statistics were presented with frequency, percentage, mean, standard deviation (SD), median, minimum (min.), and maximum (max.) values. Fisher’s Exact Test and Pearson chi-square test were used to analyze the relationships between categorical variables. Kolmogorov Smirnov test was used for the distribution of numerical measurements.
T-test, Mann Whitney U test, ANOVA, and Sidak test were used for comparison of the groups.
The cutoff value for significance was accepted as 0.05 in the study.
Results
Demographic-clinical features of the patients A total of 50 patients supported by mechanical ventilation because of sepsis were included in the study. Of these patients, 26 (52%) were male and the mean age was 66.58±5.25 years (Table 1). The mean fluid intake of the patients was 3481.8±1002.7 milliliter (ml) and the mean output was 1877.6±921.3 ml. Of the patients, 42 (84%) were in positive fluid balance, 6 (12%) were in negative fluid balance and 2 (4%) were in balance. The mean intensive care unit stay length was 9.80±7.14 days and the mean mechanical ventilation duration was 7.50±3.24 days. The mean APACHE II score, GCS, and
Table 1. Baseline characteristics of the patients
All n=50
Age (mean±SD) 66.58±5.25
Gender (n; %) MaleFemale
26 (52%) 24 (48%) Comorbidities (n; %)
DMCOPD HTOther
11 (27.5%) 8 (16.33%) 13 (32.5%) 8 (16.33%) Fluid balance
Positive Negative Balance
42 (84%) 6 (12%) 2 (4%) Fluid intake ml (mean±SD)
Fluid output 3481.88±1002.68
1877.62±921.25 Diuretic drug use
YesNo
49 (%98) 1 (2%) Vasoactive support (%)
YesNo
49 (98%) 1 (2%) Steroid
YesNo
35 (70%) 15 (30%) Sedative drug use
YesNo
47 (94%) 3 (6%) MV modality
A/CSpontaneous
38 (76%) 12 (24%) Mechanical ventilation settings (mean±SD)
FiO2PEEP Frequency Tidal Volume ml
48.37±11.39 4.75±1.49 14.93±3.05 458.54±51.18 Weaning
YesNo
12 (24%) 38 (76%) GCS (mean±SD)
APACHE II SOFA
6.7±2.2 25.9± 4.7 7.9±1.9 Survivor
nonsurvivor 5 (10%)45 (90%)
DM: Diabetes Mellitus, COPD: Chronic Obstructive Pulmonary Disease, HT: Hypertension
MV: Mechanical Ventilation. FiO2: Fraction of inspired oxygen. PEEP: Positive End Expiratory Pressure. GCS: Glasgow coma score APACHE II: Acute physiology and chronic health evaluation II, SOFA: Sequential organ failure assessment, N: Number, Sd: Standart deviation
Among the biochemical blood tests, C- reactive protein (CRP) was significantly higher (p=0.003) and albumin level was significantly lower (p=0.034) in patients with positive fluid balance than those with a negative balance (Table 2).
There was no significant difference in creatinine level between the fluid balance subgroups. The diuretic use was significantly more common in patients with positive fluid balance than those
with a negative balance (p=0.02). There was no significant difference in mechanical ventilation setting features (FiO2, PEEP, frequency, tidal volume) and in APACHE II, GCS, SOFA scores, between the fluid balance subgroups. There was no significant difference in the fluid balance between survivors and nonsurvivors.
Survivors and nonsurvivors were similar in respect to gender and comorbidity but the Table 2. Demographic and clinical features of the patients according to fluid balance
Fluid balance
Positive Fluid balance
Negative Fluid balance
Balance p
Age (mean±SD) 66.24±2.16 63.28±2.25 64.42±2.16 0.997
Creatine (mean±SD) 2.04±1.44 3.67±2.5 1.03±0.65 0.098
CRP (mean±SD) 16.52±4.62 10.84±3.4 5.49±0.95 0.003
Albumine (mean±SD) 2.47±0.36 2.85±0.2 2.70±0.43 0.034
Diuretic drug use YesNo
42 (100%)
0 5 (83.3%)
1 (16.7%) 2 (100%)
0
0.0237
Steroid use YesNo
28 (66.7%)
14 (33.3%) 6 (100%)
0 1 (50%)
1 (50%)
0.2045
Vasopressor/inotrop use YesNo
41 (97.6%)
1 (2.4%) 6 (100%)
0 2 (100%)
0
0.9074
Central Venous Pressure
(mean±SD) 11.09±2.91 10.33±1.0 - 0.772
GCSAPACHE II SOFA
6.66±2.33 26.37±4.54 7.91±1.89
6.43±1.0 25.19±4.83 8.22±1.17
8.93±0.81 20.41±6.24 5.53±2.16
0.221 0.255 0.296 Mechanical ventilation settings
(mean±SD) FiO2PEEP Frequency Tidal Volume ml
48.63±12.08 4.72±1.46 14.84±3.14 455.29±52.28
49.09±7.13 5.49±1.42 14.58±2.53 466.67±40.82
40.74±1.04 3.21±1.71 18.03±0.04 530.00±38.03
0.276 0.230 0.291 0.255 Weaning
YesNo
11 (26.2%)
31 (73.8%) -
100 1 (50%)
1 (50%)
0.25
Mechanical ventilation duration 9.20±1.34 9.44±2.24 9.10±1.36 0.534 Intensive care unit stay duration 10.60±1.88 10.34±3.46 10.95±1.20 0.644 Survivor
nonsurvivor 3 (7.1%)39 (92.9%) 1 (16.7%)5 (83.3%) 1 (50%)1 (50%) 0.1205
CRP: C-reactive protein. FiO2: Fraction of inspired oxygen. PEEP: Positive End Expiratory Pressure. GCS: Glasgow coma score APACHE II: Acute physiology and chronic health evaluation II, SOFA: Sequential organ failure assessment
survivors were significantly older than the and nonsurvivors (p=0.0001). There was no
Discussion
In our study, we observed that fluid balance had no significant effect on the length of ICU stay and on both the mechanical ventilation duration and the settings. The assessment tests for the severity and the prognosis of the disease, such as APACHE II, SOFA, and GCS were not significantly different between the fluid balance subgroups. Based on this finding, we suggest that the results of these tests in the first 24-hour could not predict the fluid balance or requirements. Additionally, we found that diuretic drugs were more frequently used and CRP was significantly higher while albumin was lower in patients with positive fluid balance than in those with negative fluid balance. There was no significant difference in fluid balance between survivors and nonsurvivors. The survivors required fewer vasoactive drugs and all the survivors were supported with spontaneous mechanical ventilator mode. Among the disease severity assessment tests (APACHE II, GCS, SOFA), only APACHE II was significantly higher in nonsurvivors than the survivors.
The fluid balance is the basis of critical patient management in the intensive care unit. In sepsis and septic shock, characterized by infection- related organ dysfunction, hypoperfusion, and low blood pressure, fluid replacement is often required at high volumes to cope with organ hypoperfusion and hypotension. However, microvascular endothelial injury related to sepsis increases the extravasation of intravascular fluid, which may result in pulmonary edema.
The effects of positive fluid balance on patients are controversial. In a previous study, no relationship was found between positive fluid balance and weaning [5]. Similarly, we did not find a significant difference in weaning between the patients with positive fluid balance and the patients with negative fluid balance. Moreover, we found that there was no significant difference in the duration of mechanical ventilation and intensive care unit stay. But contrary to our study, Diaz et al. [6] reported that the positive fluid balance was associated with the duration of mechanical ventilation and the duration of intensive care stay. This difference may be related to the participants in their study because Table 3. Demographic and clinical features of the survivors and nonsurvivors
Survivor
n=5 Non-survivor
n=45 p-value
Age (mean±SD) 75.40±7.37 61.56 ±3.73 0,021
Gender (n; %) MaleFemale
2 (40%)
3 (60%) 24 (53.33%)
21 (46.67%)
0.6613
Comorbidities (n; %) DMCOPD
HTOther
--
2 (66.67%) 1 (33.33%)
11 (29.73%) 8 (21.62%) 11 (29.73%) 7 (18.92%)
0.3926
Fluid balance Positive Negative Balance
3 (60%) 1(20%) 1(20%)
39 (86.67%) 5 (11.11%) 1 (2.22%)
0.1205
Vasoactive support (%) YesNo
4 (80%)
1 (20%) 45 (100%)
-
0.0024
MV modality A/CSpontaneous
-5 (100%) 38 (84.44 %)
7 (15.56%)
0.0001
GCS 9.00±2.45 6.78±2.02 0.067
APACHE II 20.40±4.62 25.98±4.27 0.026
SOFA 6.40±1.95 7.11±1.65 0.497
DM: Diabetes Mellitus, COPD: Chronic Obstructive Pulmonary Disease, HT: Hypertension, MV: Mechanical Ventilation GCS: Glasgow coma score, APACHE II: Acute physiology and chronic health evaluation II,
SOFA: Sequential organ failure assessment, N: Number, Sd: Standart deviation
they performed this research in children, not in adults.
Although the treatment options for sepsis and septic shock are improved every day, the mortality rate is still over 50%. There are some scoring systems that can predict the mortality rate and prognosis, like APACHE II, SOFA, and GCS. Significant long mechanical ventilation and weaning failure were detected in patients with high APACHE II scores at the time of intensive care unit admission and it was previously reported to be lower in sepsis-survivors than in sepsis-non-survivors [7-9]. Moreover, APACHE, and SOFA scores, within the first 24 hours of intensive care unit admission, were higher in nonsurvivors in a recent study [10]. In order to estimate the mortality rate in patients with sepsis, the APACHE II score is the one that is strongly recommended [11]. Wang et al. [12]
reported that both SOFA and APACHE II score, are independent prognostic factors in sepsis. In our study, we observed that only the APACHE II score was significantly higher in survivors than in the nonsurvivors. Based on this finding, we suggest that APACHE II may be better in predicting mortality, than SOFA and GCS.
Moreover, there was no significant difference between the creatine levels of the patients in respect to fluid balance in our study. Similarly, De Oliveira FSV et al. [13] reported no association between positive fluid balance and acute renal failure. But the need for diuretic drugs was significantly more common in patients with positive fluid balance than those with negative fluid balance in our study. Recently, loop diuretic was not associated with severe acute renal damage [14]. Based on these findings, the diuretic drug requirement seems to be high in patients with positive fluid and can be safely applied without increasing creatine levels.
The other significant difference between the patients with positive fluid balance and those with negative balance was the albumin level in our study. The albumin levels in patients with positive fluid balance were significantly lower
Previously, hypoalbuminemia was associated with mortality and prolonged mechanical ventilation [15, 16]. Although, statistically not significant we also observed in our study that albumin levels tended to be lower in survivors than in nonsurvivors.
Furthermore, we observed that there was no significant difference in the fluid balances of survivors and nonsurvivors. Similarly, no association was reported between the fluid intake within the first 24 hours and 90 days mortality previously [17, 18]. However, there are some reports contrary to these studies [2, 19, 20]. Recently, the negative fluid balance was associated with lower mortality [21]. Positive fluid balance was independently associated with mortality in sepsis accompanied by ARDS in another study [12]. The reason for the difference in our result about the effect of fluid balance on survival may be the small number of survivors. While the effect of positive fluid balance on survival remains uncertain, recently, it was reported that fluid replacement therapy applied according to hemodynamic parameters provided less fluid burden but didn’t reduce the total 30-day mortality [19].
There are some limitations to our study.
Major limitations are the small sample size and missing data. The number of patients in survivor and nonsurvivor subgroups and the number of patients in positive and negative/balanced fluid balance subgroups were very different and quite a few. In order to avoid obvious numerical differences between subgroups, the study parameters should be investigated prospectively and with sufficient number of patient subgroups. Moreover, in this study, the survivor group and the nonsurvivor group were not similar in respect to age. We don’t know whether the positive fluid balance is the cause or the effect with respect to all these parameters. Lastly, there may be many different parameters that may affect survival, and some of these parameters may be overlooked based on the retrospective study design.
they can be safely applied as needed in patients with sepsis. Only APACHE II was significantly higher in nonsurvivors, so seems to be better in predicting mortality than SOFA and GCS.
This was a retrospective study from a tertiary hospital, with significant numerical difference between patient subgroups. The findings of the study need to be supported by better designed, randomized, controlled prospective studies.
Conflict of interest: No conflict of interest was declared by the authors.
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Ethics committee approval: Approval was obtained from Akdeniz University Faculty of Medicine Clinical Research Ethics Committee Presidency with the date of 11.12.2019 and the number 1165.
Contributions of the authors
D.S., H.D. and A.E. set up the main idea and hypothesis of the study. H.D. and D.S.
developed the main idea and organized the materials and methods section. D.S. and H.D.
evaluated the data in the results section and wrote the discussion section of the article.
A.E. reviewed the article and made necessary corrections. In addition, all authors discussed the entire study and approved its final version.
